Submissions for variant NM_001040113.2(MYH11):c.5822A>G (p.Gln1941Arg)

gnomAD frequency: 0.00001  dbSNP: rs761957202

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000203125	SCV000257762	uncertain significance	Aortic aneurysm, familial thoracic 4	2015-06-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001189909	SCV001357293	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-03-09	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1941 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/243548 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000203125	SCV001407351	uncertain significance	Aortic aneurysm, familial thoracic 4	2022-07-25	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1941 of the MYH11 protein (p.Gln1941Arg). This variant is present in population databases (rs761957202, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 218497). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001775667	SCV002012842	uncertain significance	not provided	2021-08-28	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV001775667	SCV004141208	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing	MYH11: PM2, BP4
All of Us Research Program, National Institutes of Health	RCV001189909	SCV004815477	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-07-29	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1941 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/243548 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.